Expression of cytokine genes or proteins and signaling molecules in lymphocytes associated with human ovarian carcinoma

We have reported that tumor‐associated T or natural killer (NK) lymphocytes purified from ascites of women with ovarian carcinoma show defective expression and function of signaling proteins, including reduced expression of TcR‐ζ chains and p56 lck . In this study, the cytokine profiles of both tumor cells and tumor‐associated lymphocytes (TAL) recovered from the tumor milieu were examined. Expression of cytokine genes was studied by semi‐quantitative RT‐PCR and Southern hybridization, and the presence of intracellular cytokine proteins was confirmed by immunostaining. Levels of mRNA encoding the cytokine genes typically transcribed in activated T lymphocytes, including IFN‐γ, IL‐2 and IL‐4, were markedly reduced, as was expression of the corresponding proteins, in TAL‐T or TAL‐NK cells relative to normal PBL‐T or PBL‐NK cells, respectively. Levels of TGF‐β and IL‐6 were unaltered, while those of IL‐10 were up‐regulated. Although both tumor cells and TALs contributed to the enhanced level of IL‐10 expression, a higher proportion of TAL‐T lymphocytes than normal PBL‐T cells expressed IL‐10 protein. The altered profile of cytokine genes and proteins in TALs, TAL‐T or TAL‐NK cells was associated with impaired expression and/or function of signaling molecules, ζ chain and p56 lck . Our data suggest that abnormalities in signal transduction commonly seen in lymphocytes obtained from the tumor micro‐environment are related to the concomitantly observed altered patterns of expression of cytokine transcripts and proteins. © 1996 Wiley‐Liss, Inc.